The Role of Corticotropin-Releasing Factor in Primate Maternal Behavior

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DESCRIPTION (provided by applicant): In women, both stress and a number of stress-related psychopathological conditions, including major depressive disorder, postpartum depression, and post-traumatic stress disorder, can lead to impaired maternal behavior and increased likelihood of child abuse. The mechanisms by which stress and stress- related psychopathology disrupt maternal behavior are not known. Both stress and stress-related psychopathology, however, are commonly associated with hyperactivity of the brain's corticotropin-releasing factor (CRF) systems. In rodents, stress increases expression of CRF in behaviorally relevant nuclei, and CRF has been shown to disrupt maternal behavior and increase rates of infant-killing. Moreover, elevated CRF concentrations in the brain correlate with impaired maternal behavior in primates. This research will develop the marmoset monkey as a novel primate mode! in which to investigate the mechanisms of stress- related deficits in maternal behavior. In addition, it will test the hypothesis that high levels of CRF can disrupt maternal behavior in primates. The specific aims are to (1) characterize the effects of acute stress and a CRF type-1 receptor antagonist on maternal behavior, (2) determine whether intracerebroventricular administration of CRF inhibits maternal behavior, and (3) characterize the distribution of CRF, CRF type-1 receptor, and CRF-binding protein in the marmoset brain, and determine the effects of acute stress on this system. These studies will elucidate the relationships among stress, stress-related psychopathology, and maternal behavior in primates and will lay the essential foundations for subsequent studies of the effects of both chronic and acute stress on maternal and abusive behavior. Thus, this work will make a significant contribution to our understanding of the neurobiology of maternal behavior in primates, including humans. Relevance: Stress, as well as stress-related mood and anxiety disorders, can impair maternal behavior and increase the likelihood of child abuse; however, the mechanisms are not known. This research will develop the marmoset as a new primate model for understanding the effects of acute and chronic stress on maternal behavior and will begin to identify the underlying mechanisms. Ultimately, this research will have implications for the understanding and treatment of stress-related psychopathology in women.